DESCRIPTION: (Verbatim from the Applicant's Abstract) The goal of this research is to understand the role of mitochondrial dysfunction and oxidative stress in Parkinson's disease (PD). These experiments will utilize both a novel in viovo model of PD as well a a cell culture model to elucidate the mechanisms by which complex I inhibition and oxidative damage result in neuronal cell death. Chronic, systemic rotenone treatment to rats will be used as a model of complex I dysfunction and selective nigrostriatal dopaminergic neurodegeneration seen in PD. Specifically, levels of aoxidative stress will be determined biochemically using an oxyblot technique. Regional distribution of oxidative damage will be studied using immunocytochemical protocols. Additionally, a c ell culture model in which cells are treated chronically with sublethal doses of rotenone will be used. In this system, we will use fluorescent techniques to determine whether chronic complex I dysfunction increases the susceptibility to cell death following exposure to apoptogenic agents. Finally, we will test new potential therapeutic agents for PD such as the antioxidant, coenzyme Q10 that also enhances mitochondrial function.